Monoclonal Antibodies
The first monoclonal antibody-producing hybridomas were the results of techniques devised by Kohler and Milstein (G. Kohler and C. Milstein, 1975, Nature 256: 495-497; 1976 Eur. J. Immunol. 6: 511-519). By fusing antibody forming cells with myeloma cells, Kohler and Milstein created a hybrid cell line arising from a single-fused cell hybrid which had inherited certain characteristics of both the lymphocytes and the myeloma cell lines. Like lymphocytes, the hybridomas secrete a single type of immunoglobulin specific to the antigen. Like the myeloma cells, the hybrid cells have the potential for indefinite cell division. The combination of these two features offer distinct advantages over conventional antisera. Conventional antisera derived from vaccinated animals is a heterogeneous mixture of polyclonal antibodies which cannot be reproduced identically whereas monoclonal antibodies are specific, homogeneous immunoglobulins derived from a single hybridoma cell. Any given clone produces identical antibodies. The hybridoma cell line is easily propagated in vitro or in vivo to yield monoclonal antibodies in extremely high concentrations. The hybridoma secretes an immunoglobulin specific to one and only one antigenic determinant, or epitope, on the antigen, a complex molecule having a multiplicity of antigenic determinants. For example, if an antigen is a protein, the antigenic determinant may be one of many peptide sequences, of approximately six to seven amino acids in length, within the entire protein of the molecule. Monoclonal antibodies thereby raised against a single antigen may be distinct from each other depending on the determinant that stimulated their formation.
Up until this time, several diagnostic methods have been devised to measure the in vivo concentrations of fibrin, fibrinogen and their derivatives for the diagnosis and treatment of vascular disorders, such as deep vein thrombosis and disseminated intravascular coagulation. Many of these diagnostic methods have been devised based on the production of polyclonal antisera to fibrin and fibrinogen derivatives. With the advent of hybridoma technology, monoclonal antibodies have been designed to be directed to individual antigenic sites. However, reports indicate that the problem in trying to produce an antisera remains to be a lack of specificity due to the relatively small differences between fibrinogen and fibrin and the number of neoantigenic sites, which is the inherent problem of producing antisera specific to fibrin, fibrinogen and their derivatives.